The Vector Core Facility (Core B) will manufacture all the recombinant adenovirus (rAd) vaccines for the preclinical studies and the clinical trials described in this IPCAVD grant. Crucell Holland BV is a medium-sized biotechnology company that is dedicated to the development of vaccines for infectious diseases. In particular, Crucell has pioneered the development of rAd vector-based vaccines and has developed vaccine vectors from several Ad serotypes that have low seroprevalence in human populations. Crucell has also been a leader in the preclinical-to-clinical translational development of rAd vector-based vaccines. In particular, Crucell has developed robust production and purification methods to manufacture clinical-grade rAd vaccines that conform to all FDA and EC requirements, standardized and validated release assays, and developed several packaging cell lines that support pharmaceutical-scale manufacturing. Centralized production, purification, and quality control standards are critical to ensure the quality of the rAd vector-based vectors that will be used in the vaccine studies in this IPCAVD grant. This Core Facility will produce the research-grade rAd vaccines to support the preclinical studies described in Projects 1 and 2 and the clinical-grade rAd vaccines to support the clinical trials described in Project 2. We propose the following three Specific Aims for this Core Facility: 1. To manufacture, purify, and quality control research-grade rAd vaccines expressing HIV-1 and SIV antigens;2. To manufacture, purify, quality control, and release clinical-grade rAd vaccines expressing HIV-1 antigens under Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP) conditions;and 3. To coordinate preclinical toxicology studies under GLP conditions and prepare IND applications to support the initiation of phase I and phase II clinical trials.